Methods, systems, and devices relating to open microfluidic channels

ABSTRACT

Various collection devices, systems and methods relating to the use of devices with open microfluidic channels disposed within a housing defining a lumen. These devices make use of microneedles passed through apertures to induce fluid flow into microfluidic channel networks for collection and analysis. The device can be actuated via button when placed on the skin of a patient to collect a fluid sample, such as a blood draw.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Patent Application No.16/671,492, filed Nov. 1, 2019, and titled “METHODS, SYSTEMS, ANDDEVICES RELATING TO OPEN MICROFLUIDIC CHANNELS,” which is a continuationof U.S. Pat. Application No. 15/951,854, filed Apr. 12, 2018, and titled“METHODS, SYSTEMS, AND DEVICES RELATING TO OPEN MICROFLUIDIC CHANNELS,”now issued as U.S. Pat. No. 10,492,716, which is a continuation of U.S.Pat. Application No. 13/750,526, filed Jan. 25, 2013, and titled“HANDHELD DEVICE FOR DRAWING, COLLECTING, AND ANALYZING BODILY FLUID,”which claimed priority to U.S. Provisional Pat. Application No.61/590,644, filed Jan. 25, 2012, and titled “HANDHELD DEVICE FORDRAWING, COLLECTING, AND ANALYZING BODILY FLUID,” and is also acontinuation of U.S. Pat. Application No. 14/932,485, filed Nov. 4,2015, and titled “METHODS, SYSTEMS, AND DEVICES RELATING TO OPENMICROFLUIDIC CHANNELS,” now issued as U.S. Pat. No. 9,987,629, which isa continuation of U.S. Pat. Application No. 13/949,108, filed Jul. 23,2013, and titled “METHODS, SYSTEMS, AND DEVICES RELATING TO OPENMICROFLUIDIC CHANNELS,” now issued as U.S. Pat. No. 9,289,763, whichclaims priority to U.S. Pat. Provisional Application No. 61/674,415,filed Jul. 23, 2012, and titled “METHODS, SYSTEMS, AND DEVICES RELATINGTO OPEN MICROFLUIDIC CHANNELS,” each of which is herein incorporated byreference in its entirety.

TECHNICAL FIELD

The disclosed technology relates to various methods, systems, anddevices regarding fluid handling for medical devices, and in particular,interfacing bodily fluids with a microfluidic network and the subsequenthandling of the fluid in order to direct it towards diagnostic sensingor biomarker analysis components.

BACKGROUND

An open microchannel is defined as a microfluidic channel whosecross-section is composed of solid walls as well as at least one sectionwith open liquid-air interface. Open microchannels present advantageousproperties linked to their reliability, function, and manufacturability.Open microchannels solve a problem related to air bubbles, as the gascan escape through the open face of the channel, thus creating a devicethat is more reliable in comparison to traditional closed channelsetups. However, prior to the inventions described herein, flow in openmicrofluidic channels was not well understood, and the few existingmethods demonstrated until now have had limited functionality, namelytransporting fluid for a short distance in a straight line, as describedin the filed patents 11/470,021 and 09/943,080. A second problem inexisting technology relating to open microfluidic channels was the lackof ability to control the flow of fluid, thus preventing the creation ofadvanced fluid handling platforms designed entirely or in large partbased on that technology. Thirdly, there was, prior to the inventionsdescribed herein, a lack of tools allowing for the insertion of fluidinto, or removal of fluid from, the open channel. All of the knownmethods relied on dipping a single device into the liquid of interest inorder to sample a small amount, rather than having the ability to createnetworks in which fluid can be inserted at precise locations and atdifferent times. Further, no known method prior to the inventionsdescribed herein provides for the removal of fluid from these channels.Thus, there is a need in the art for improved open microfluidic channelsand related systems, devices, and methods.

SUMMARY

The disclosed apparatus, systems and methods relate to the benefits inthe manufacturing of shallow open microchannels, as this can beperformed in one single molding or embossing step as it does not requirebonding to enclose the channel, enabling large scale manufacturing ofcomplex networks at low costs. These advantages make open microchannelnetworks particularly well suited for disposable diagnostic devices forwhich fluids require precise handling with low manufacturing costs. Thisdocument describes a set of methods and embodiments that facilitate newmethods for handling fluid or bodily samples and enable the interfacingwith microfluidic networks in new ways. The preferred embodiment of theapproaches described is for use in medical devices, at-home diagnosticdevices, and laboratory analysis platforms.

Certain examples shall now be described.

In Example 1, a microfluidic device comprises a first microscaled, ormicrofluidic channel configured to allow flow of fluids by capillaryaction, wherein the channel has at least one portion of the channelcomprising a first cross-section. The first cross-section comprises awetted surface comprising hydrophilic material and a free interfacecomprising an open air-liquid interface. The wetted surface contactsfluid flowing through the channel. The ratio of a cross-sectional lengthof the free interface and a cross-sectional length of the wetted surfaceis less than the cosine of the contact angle, thereby permittingspontaneous capillary flow.

Example 2 relates to the microfluidic device according to Example 1,wherein the first cross-section further comprises at least two wettedsurfaces, and an interface with a high contact angle, a hydrophobicarea, or a second free liquid-air interface.

Example 3 relates to the microfluidic device according to Example 2,wherein the first cross-section comprises a rectangular or trapezoidalshape, wherein the free interface comprises a first free interfacedefined in a top portion of the first cross-section and a second freeinterface defined in a bottom portion of the first cross-section.

Example 4 relates to the microfluidic device according to Example 1,wherein the free interface is defined in a bottom portion of the devicesuch that the free interface can be brought into contact with a volumeof fluid pooling on a surface, thereby causing capture of at least aportion of the volume and flow of the volume into the channel.

Example 5 relates to the microfluidic device according to Example 1,wherein the first microscale channel further comprises a second freeinterface comprising an open air-liquid interface or an insert ofoptically transparent material, wherein the first channel is configuredto allow flow of fluid over the second free interface, and wherein thesecond free interface defines a light path configured to allow light tostrike the fluid in the channel in order to perform a fluorescence orspectrometry analysis of the fluid.

Example 6 relates to the microfluidic device according to Example 1,wherein the open air-liquid interface is configured to provide accessfor the removal of a fluid sample from the channel or any component ofthat fluid sample.

Example 7 relates to the microfluidic device according to Example 6,wherein the open air-liquid interface is configured to receive a secondcapillary channel, thereby allowing the fluid flow into a second fluidicnetwork.

Example 8 relates to the microfluidic device according to Example 1,wherein the first channel further comprises a second cross-section thatcomprises a first configuration and a second configuration. The firstconfiguration has a ratio of a cross-sectional length of a freeinterface and a cross-sectional length of a wetted surface that isgreater than the cosine of the contact angle, thereby preventingspontaneous capillary flow. The second configuration has a ratio of thecross-sectional length of the free interface and a cross-sectionallength of the wetted surface that is less than the cosine of the contactangle.

Example 9 relates to the microfluidic device according to Example 8,further comprising a conversion mechanism configured to convert thesecond cross-section from the first configuration to the secondconfiguration and from the second configuration to the firstconfiguration.

Example 10 relates to the microfluidic device according to Example 9,wherein the conversion mechanism comprises a presence or absence of animmiscible fluid over at least part of the open air-liquid interface ofthe second cross-section, such that the immiscible fluid constitutes aportion of the wetted surface.

Example 11 relates to the microfluidic device according to Example 11,wherein the conversion mechanism comprises a solid material configuredto move between a position non-adjacent to the first channel and aposition coupled with the first channel, such that the materialconstitutes a portion of the wetted surface.

Example 12 relates to the microfluidic device according to Example 9,wherein the conversion mechanism comprises movement of the walls of thefirst channel between the first configuration and the secondconfiguration.

Example 13 relates to the microfluidic device according to Example 1,wherein the channel comprises a material configured to remove at least aportion of the fluid.

Example 14 relates to the microfluidic device according to Example 13,wherein the channel comprises an aperture defined in the channel,wherein the aperture provides fluid access to an external environment.

Example 15 relates to the microfluidic device according to Example 13,wherein the material comprises a hydrogel, paper, or anotherliquid-absorbent material.

Example 16 relates to the microfluidic device according to Example 13,wherein the material comprises an inorganic phase, an organic solvent,an antibody-laden hydrogel or another analyte-extracting material.

Example 17 relates to the microfluidic device according to Example 1,wherein the channel is configured to enable flow at any angle relativeto horizontal.

Example 18 relates to the microfluidic device according to Example 1,wherein the channel is defined along a surface of a needle.

Example 19 relates to the microfluidic device according to Example 18,wherein the first channel is coupleable to a second microscale channelon a surface of a base that is coupleable to the needle.

Example 20 relates to the microfluidic device according to Example 1,wherein a ratio of the cross-sectional length of the free interface tothe cross-sectional length of the wetted surface decreases along alength of the first channel, whereby a droplet of fluid added to aninlet of the channel is self-propelled along the length of the firstchannel.

Example 21 relates to the microfluidic device according to Example 1,further comprising a second cross-section and a transition between thefirst and second cross-sections. The second cross-section is greater insize in comparison to the first cross-section. The transition causespinning of the flow of fluids, such that the flow is only enabled whenliquid is provided downstream of the geometry change.

Example 22 relates to the microfluidic device according to Example 1,wherein the first channel is in fluid communication with a common area,wherein at least one additional channel is also in fluid communicationwith the a common area, thereby allowing device filling independent ofsynchronized fluid additions.

Example 23 relates to the microfluidic device according to Example 1,wherein the first channel comprises material positioned on a surface ofthe first channel, whereby the material is configured to incorporateinto solution when a fluid flows through the first channel.

In Example 24, a method for using a microscale channel comprisesproviding fluid to or removing fluid from a first microscale channel.The first channel comprises a first cross-section that comprises awetted surface comprising hydrophilic material and a free interfacecomprising an open air-liquid interface. The wetted surface contactsfluid flowing through the channel. The ratio of a cross-sectional lengthof the free interface and a cross-sectional length of the wetted surfaceis less than the cosine of the contact angle, thereby permittingspontaneous capillary flow.

Example 25 relates to the method according to Example 24, wherein theproviding fluid to the first microscale channel comprises inserting thefluid in the first channel with an automated fluid dispensing system.

Example 26 relates to the method according to Example 25, wherein theautomated fluid dispensing system is a manual or automated pipette.

Example 27 relates to the method according to Example 24, wherein theproviding fluid to the first microscale channel comprises contacting thefirst channel with a fluid pooling on a surface, thereby drawing thefluid into the first channel.

Example 28 relates to the method according to Example 27, wherein thefluid is blood and the surface is the surface of the skin.

Example 29 relates to the method according to Example 24, wherein theremoving the fluid from the first microscale channel comprises placingthe first channel in fluid communication with a second channel, whereinthe second channel has a second cross-section with a ratio of across-sectional length of a free interface to a cross-sectional lengthof a wetted surface that is smaller than the ratio of the firstcross-section.

Example 30 relates to the method according to Example 24, wherein theproviding fluid to the first microscale channel comprises placing an endof the first channel into a second channel, wherein the second channelhas a second cross-section with a ratio of a cross-sectional length of afree interface to a cross-sectional length of a wetted surface that isgreater than the ratio of the first cross-section.

Example 31 relates to the method according to Example 24, wherein theremoving the fluid from the first microscale channel comprises removinga substance from the fluid through an open air-liquid interface windowdefined in the channel.

Example 32 relates to the method according to Example 31, wherein theremoving the substance from the fluid comprises removing magnetic beadsby applying a magnetic force at the window.

Example 33 relates to the method according to Example 32, wherein theremoving the magnetic beads comprises trapping the beads on a solidsurface by placing the solid surface in substantially proximity with orin contact with the surface of the liquid at the window.

Example 34 relates to the method according to Example 31, wherein theremoving the substance from the fluid comprises extracting particlesfrom the fluid by contacting the fluid with an immiscible fluid at thewindow.

Example 35 relates to the method according to Example 31, whereinremoving the substance from the fluid comprises removing particles bytrapping the particles on a material placed in contact with the fluidinterface at the window, wherein the material comprises compoundsconfigured to bind the particles.

In Example 36, a method for using a microscale channel comprises movingfluid within a first microscale channel. The first channel comprises afirst cross-section that comprises a wetted surface comprisinghydrophilic material and a free interface comprising an open air-liquidinterface. The wetted surface contacts fluid flowing through thechannel. The ratio of a cross-sectional length of the free interface anda cross-sectional length of the wetted surface is less than the cosineof the contact angle, thereby permitting spontaneous capillary flow.

Example 37 relates to the method according to Example 36, wherein themoving fluid within the first channel comprises urging fluid through thefirst channel and at least one other channel into a common channel orholding chamber, wherein flow within each of the first channel and theat least one other channel are independent, thereby allowing acombination of different flows without air bubble formation.

Example 38 relates to the method according to Example 36, wherein thefirst channel comprises a flow control location comprising a flowcontrol cross-section comprising a ratio of free interface to wettedsurface that is greater than the cosine of the contact angle, the methodfurther comprising reducing the ratio of the flow control cross-sectionto a value smaller than the cosine of the contact angle.

Example 39 relates to the method according to Example 38, wherein thereducing the ratio of the flow control cross-section further comprisesadding an immiscible fluid to the channel such that the immiscible fluidspans a portion of the free interface of the first channel.

Example 40 relates to the method according to Example 38, wherein thereducing the ratio of the flow control cross-section further comprisesdisplacing a material that covers a portion of the free interface of thefirst channel.

Example 41 relates to the method according to Example 38, wherein thereducing the ratio of the flow control cross-section further comprisesdisplacing at least one wall of the first channel, thereby reducing alength of the free interface.

Example 42 relates to the method according to Example 36, wherein themoving the fluid within the first channel further comprises causing thefluid to flow on a first plane oriented at any angle, and causing thefluid to traverse to a second plane with a connector oriented at anyangle relative to the first plane.

Example 43 relates to the method according to Example 42, wherein theconnector comprises an open microfluidic channel having only two wettedsurfaces.

Example 44 relates to the method according to Example 36, wherein themoving the fluid within the first channel further comprises causing thefluid to flow over a heterogeneous area disposed on a wall of the firstchannel.

Example 45 relates to the method according to Example 44, wherein thearea is an open liquid-air interface.

Example 46 relates to the method according to Example 44, wherein thearea is an absorbent material, thereby causing the absorption of adefined fluid volume.

Example 47 relates to the method according to Example 44, wherein thearea is a second immiscible fluid.

Example 48 relates to the method according to Example 36, wherein themoving the fluid within the first channel further comprises causing thefluid to flow over an opening in a bottom portion of the first channelsuch that the fluid is in fluid communication with ambient air on a topportion and the bottom portion of the first channel.

Example 49 relates to the method according to Example 36, wherein themoving the fluid within the first channel further comprises applying areagent in dried form on the surface of the first channel such that thereagent dissolves into the fluid as the fluid is moved through thechannel.

Example 50 relates to the method according to Example 36, wherein themoving the fluid within the first channel further comprises coating atleast a portion of at least one wall of the first channel with areagent, wherein the reagent comprises particles of interest.

While multiple embodiments are disclosed, still other embodiments of thepresent invention will become apparent to those skilled in the art fromthe following detailed description, which shows and describesillustrative embodiments of the invention. As will be realized, theinvention is capable of modifications in various obvious aspects, allwithout departing from the spirit and scope of the present invention.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of an exemplary embodiment of amicrochannel containing an open interface.

FIG. 1B is a perspective view of an exemplary embodiment of amicrochannel containing an open interface.

FIG. 1C is a perspective view of an exemplary embodiment of amicrochannel containing an open interface.

FIG. 1D is a perspective view of an exemplary embodiment of amicrochannel containing an open interface.

FIG. 1E is a sidelong view of an exemplary embodiment of a microchannelcontaining an open interface.

FIG. 1F is a sidelong view of an exemplary embodiment of a microchannelcontaining an open interface.

FIG. 1G is a sidelong view of an exemplary embodiment of a microchannelcontaining an open interface.

FIG. 1H is a perspective view of an exemplary embodiment of amicrochannel containing an open interface.

FIG. 2A is a perspective view of an exemplary embodiment of amicrofluidic channel used to collect fluid pooling on a surface.

FIG. 2B is a perspective view of an exemplary embodiment of amicrofluidic channel used to collect fluid pooling on a surface.

FIG. 2C is a perspective view of an exemplary embodiment of amicrofluidic channel used to collect fluid pooling on a surface.

FIG. 2D is an underside perspective view of a microfluidic channel usedto collect fluid pooling on a surface according to an exemplaryembodiment.

FIG. 3A is a perspective view of an open microfluidic channel with anopen interface used to extract particles in fluid or a portion of thefluid itself from the channel according to one exemplary embodiment.

FIG. 3B is a perspective view of an open microfluidic channel with anopen interface used to extract particles in fluid or a portion of thefluid itself from the channel according to one exemplary embodiment.

FIG. 3C is a perspective view of an open microfluidic channel with anopen interface used to extract particles in fluid or a portion of thefluid itself from the channel according to one exemplary embodiment.

FIG. 3D is a perspective view of an open microfluidic channel with anopen interface used to extract particles in fluid or a portion of thefluid itself from the channel according to one exemplary embodiment.

FIG. 4A is a perspective view of liquid in an open microfluidic channel,the liquid flowing over a heterogeneous patch in the wall of thechannel, according to certain exemplary embodiments.

FIG. 4B is a perspective view of liquid in an open microfluidic channel,the liquid flowing over a heterogeneous patch in the wall of thechannel, according to certain exemplary embodiments.

FIG. 4C is a cross-sectional view of liquid in an open microfluidicchannel, the liquid flowing over a heterogeneous patch in the wall ofthe channel, according to certain exemplary embodiments.

FIG. 4D is a cross-sectional view of liquid in an open microfluidicchannel, the liquid flowing over a heterogeneous patch in the wall ofthe channel, according to certain exemplary embodiments.

FIG. 4E is a cross-sectional view of liquid in an open microfluidicchannel, the liquid flowing over a heterogeneous patch in the wall ofthe channel, according to certain exemplary embodiments.

FIG. 5A is a perspective view of an open microfluidic channel in which amaterial is either placed in contact with the open interface section ofthe microfluidic channel or distant of it, allowing the controllableflow through the microchannel, according to one embodiment.

FIG. 5B is a perspective view of an open microfluidic channel in which amaterial is either placed in contact with the open interface section ofthe microfluidic channel or distant of it, allowing the controllableflow through the microchannel, according to one embodiment.

FIG. 5C is a perspective view of an open microfluidic channel in which aforce applied to the channel can reduce or increase the free perimeterat a certain location, thereby enabling or preventing the flow of afluid in the channel, respectively, according to one embodiment.

FIG. 5D is a perspective view of an open microfluidic channel in which aforce applied to the channel can reduce or increase the free perimeterat a certain location, thereby enabling or preventing the flow of afluid in the channel, respectively, according to one embodiment.

FIG. 6A is a perspective view of a liquid flowing in an openmicrofluidic channel starting at one plane and bringing the fluid in anopen microfluidic channel on a second plane, according to certainexemplary embodiments.

FIG. 6B is a perspective view of a liquid flowing in an openmicrofluidic channel starting at one plane and bringing the fluid in anopen microfluidic channel on a second plane, according to certainexemplary embodiments.

FIG. 6C is a cross-sectional view of a liquid flowing in an openmicrofluidic channel starting at one plane and bringing the fluid in anopen microfluidic channel on a second plane, according to certainexemplary embodiments.

FIG. 7A is a perspective view of an open microchannel defined in aneedle that connects into a second open microfluidic channel at the baseof the needle, according to one exemplary embodiment.

FIG. 7B is a perspective view of an open microchannel defined in aneedle that connects into a second open microfluidic channel at the baseof the needle, according to the exemplary embodiment of FIG. 7A.

FIG. 8A is a perspective view of an exemplary embodiment of an openmicrofluidic channel with cross-sections that progressively narrow,according to an exemplary embodiment.

FIG. 8B is a perspective view of an exemplary embodiment of an openmicrofluidic channel with cross-sections that progressively narrow,according to an exemplary embodiment.

FIG. 8C is a perspective view of an exemplary embodiment of an openmicrofluidic channel with cross-sections that progressively narrow,according to an exemplary embodiment.

FIG. 8D is a perspective view of an exemplary embodiment of an openmicrofluidic channel with cross-sections that progressively narrow,according to an exemplary embodiment.

FIG. 8E is a perspective view of an exemplary embodiment of an openmicrofluidic channel with cross-sections that progressively narrow,according to an exemplary embodiment.

FIG. 8F is a perspective view of an exemplary embodiment of an openmicrofluidic channel with cross-sections that progressively narrow,according to an exemplary embodiment.

FIG. 8G is a perspective view of an exemplary embodiment of an openmicrofluidic channel with cross-sections that progressively narrow,according to an exemplary embodiment.

FIG. 9A is a perspective view of an open microfluidic channel withcross-sections that abruptly narrow, thereby enabling the creation of acapillary valve that does not require an air outlet to prevent theformation of air bubbles to operate, according to certain exemplaryembodiments.

FIG. 9B is a perspective view of an open microfluidic channel withcross-sections that abruptly narrow, thereby enabling the creation of acapillary valve that does not require an air outlet to prevent theformation of air bubbles to operate, according to certain exemplaryembodiments.

FIG. 9C is a perspective view of an open microfluidic channel withcross-sections that abruptly narrow, thereby enabling the creation of acapillary valve that does not require an air outlet to prevent theformation of air bubbles to operate, according to certain exemplaryembodiments.

FIG. 9D is a perspective view of an open microfluidic channel withcontrollable open capillary valve and open area, wherein the open areahas not yet filled with fluid because the fluid has pinned, according tocertain exemplary embodiments.

FIG. 9E is a perspective view of the embodiment of FIG. 9D, wherein theaddition of fluid has cause flow into the open area.

FIG. 10A is a perspective view of a Y channel allowing two sources offluid to join and in which one branch can be filled before the otherbranch without the risk of creating an air bubble, according to anexemplary embodiment.

FIG. 10B is a perspective view of a Y channel allowing two sources offluid to join and in which one branch can be filled before the otherbranch without the risk of creating an air bubble, according to anexemplary embodiment.

FIG. 10C is a perspective view of a Y channel allowing two sources offluid to join and in which one branch can be filled before the otherbranch without the risk of creating an air bubble, according to anexemplary embodiment.

FIG. 10D is a perspective view of a Y channel allowing two sources offluid to join and in which one branch can be filled before the otherbranch without the risk of creating an air bubble, according to anexemplary embodiment.

FIG. 10E is a perspective view of a Y channel allowing two sources offluid to be routed into two other channels, in which one source branchcan be filled before the other source branch without the risk ofcreating an air bubble, according to an exemplary embodiment.

FIG. 10F is a perspective view of a Y channel allowing two sources offluid to join and in which one branch can be filled before the otherbranch without the risk of creating an air bubble, according to anexemplary embodiment.

FIG. 10G is a perspective view of a Y channel allowing two sources offluid to join and in which one branch can be filled before the otherbranch without the risk of creating an air bubble, according to anexemplary embodiment.

FIG. 11A is a perspective view of a method enabling the flow of fluidsfrom one open microfluidic channel to another, according to oneembodiment.

FIG. 11B is a perspective view of an open microfluidic network builtinside a larger open microfluidic network, according to one embodiment.

FIG. 11C is a perspective view of an open microfluidic network builtinside a larger open microfluidic network, according to one embodiment.

FIG. 11D is a perspective view of the embodiment of FIG. 11C showingfluid flow.

FIG. 11E is a perspective view of an alternate embodiment of the systemwhich enables the flow of fluid from one open microfluidic channel toanother in an approach that allows the building of open microfluidicnetworks.

FIG. 11F is a perspective view of the embodiment of FIG. 11 E showingfluid flow.

FIG. 12A is a perspective view of an alternative embodiment of thesystem facilitating the flow of fluids from one open microfluidicchannel into a larger volume reservoir in an approach that allows thefilling of an open microfluidic reservoir of variable volumes that isaccessible from at least one opening.

FIG. 12B is a perspective view of the embodiment of FIG. 12A showingfluid flow.

FIG. 12C is a perspective view of the embodiment of FIG. 12A, againshowing fluid flow.

FIG. 13A is a side view of an exemplary embodiment of the systemenabling the capture of excess fluid on a surface through openmicrofluidic channels to dry or remove liquids from a surface.

FIG. 13B is a side view of another exemplary embodiment of the systemenabling the capture of excess fluid on a surface through openmicrofluidic channels to dry or remove liquids from a surface.

FIG. 14A is a perspective view of an exemplary embodiment of the systemenabling the application of a substance to an open microfluidic channelor reservoir to apply treatments to a contained fluid.

FIG. 14B is a perspective view of the embodiment of FIG. 14A, showingthe substance applied to the fluid.

FIG. 14C is a perspective view an alternative exemplary embodiment ofthe system enabling the application of a substance to an openmicrofluidic channel or reservoir to apply treatments to a containedfluid.

FIG. 14D is a perspective view of the embodiment of FIG. 14C, showingthe substance applied to the fluid.

FIG. 15 is a perspective view of the handheld device, according to oneembodiment.

FIG. 16 is an exploded front view of the handheld device, according toone embodiment.

FIG. 17 is another exploded perspective view of the handheld device,according to one embodiment.

FIG. 18 is an exploded front view of the handheld device, according toone embodiment.

FIG. 19 is an exploded cross sectional front view of the handhelddevice, according to one embodiment.

FIG. 20 is an isometric view of the bottom of the base of the handhelddevice, according to one embodiment.

FIG. 21 is a perspective view of the top of the base of the handhelddevice, according to one embodiment.

FIG. 22 is a perspective view of a portion of the top of the base of thehandheld device, according to one embodiment.

DETAILED DESCRIPTION

The various systems and devices disclosed herein relate to devices foruse in medical procedures and systems. More specifically, variousembodiments relate to various medical devices, including open devices,methods and systems relating to a microfluidic network.

It is understood that the various embodiments of the devices and relatedmethods and systems disclosed herein can be incorporated into or usedwith any other known medical devices, systems, and methods. For example,the various embodiments disclosed herein may be incorporated into orused with any of the medical devices and systems disclosed in co-pendingU.S. Application No. 13/750,526, filed Jan. 25, 2013, entitled “HandheldDevice for Drawing, Collecting, and Analyzing Bodily Fluid,” whichclaims priority to U.S. Application No. 61/590,644, filed Jan. 25, 2012,entitled “Handheld Device for Drawing, Collecting, and Analyzing BodilyFluid,” co-pending U.S. Application No. 14/932,485, filed Nov. 4, 2015,entitled “Methods, Systems, and Devices Relating to Open MicrofluidicChannels,” both of which are hereby incorporated herein by reference intheir entireties.

Exemplary implementations of the disclosed systems, devices and methodsutilize open microfluidic channels, and particularly, open microfluidicchannels capable of spontaneous capillary flow. The ability to createflow in open microfluidic channels is a required condition for creatingfunctional open microfluidic networks. As open microfluidic channelscontain open liquid-air interfaces, pressure sources are not thepreferred method to drive fluid flow; rather spontaneous capillary flowoffers a reliable, scalable driving force for fluid flow. The use ofcapillary-driven flow to manipulate fluids in complex open microfluidicnetworks is a novel feature previously unused in open microfluidicchannels.

In order to ensure that spontaneous capillary flow (SCF) occurs in achannel containing any number of open liquid-air interfaces in itscross-section, an analysis of capillary force was developed, to define adesign guideline ensuring that the capillary force provided by the wallsof the microfluidic channel overcomes the resistance created by the opensections of the microfluidic channel. The result of the analysis iswritten in a SCF relation stating that the ratio of the free perimeter(p_(f)), defined by the length of the cross-section open to air oranother medium, and the wetted perimeter (p_(w)), defined by the lengthof the cross-section made up of solid hydrophilic material must be lessthan the cosine of the contact angle (θ) of the fluid with the channelwalls. When the SCF relation is satisfied, the channel will drive theflow through the microfluidic network by capillary forces. Importantly,the SCF relation extends to most channel configurations containing openliquid-air and wetted sections. Further, the open liquid-air sections donot have to be continuous or contiguous. Thus the SCF relation stillholds for complex channel geometries containing open “windows” on thechannel (e.g. a circular aperture in the wall of a channel) as wellchannels containing multiple open liquid-air interfaces at the samepoint in the channel (e.g. a fluid completely suspended between tworails in a channel devoid of ceiling and floor). Open microfluidicchannels verifying the SCF relation also have the benefit of not beingconstrained to rectangular cross-sections. The SCF relation can bewritten in equation (1):

p_(j)/p_(w) < cos(θ)

Equation (1) represents the fundamental physical background for thedevelopment of the building blocks for the handling of fluids in openmicrofluidic networks described in the patent following. Importantly,open microfluidic methods eliminate the problem inherent inmicrofluidics of bubble formation being catastrophic within amicrochannel, and enable simplified manufacturing due to no requiredbonding to seal the channel. We have developed fluid manipulationtechniques based on open channel concepts, which are the building blocksto create a microfluidic fluid handling network amenable to human bodilyfluid collection and analysis. The two aspects covered by this inventionpertain to (1) handling fluid into and out of the microfluidic networkand (2) handling techniques within the microfluidic network.

The development of an analytical model for describing conditions of flowin open microfluidic channels has led to the establishment of anequation detailing the geometrical conditions for flow in openmicrofluidic networks and precise design guidelines that enable adramatic expansion of the functionalities of open microfluidic systems.One of the enabling aspects of such a development is the ability to flowfluids in shallow open microfluidic channels, open microfluidic channelswith non-rectangular cross-sections, non-planar and angled openmicrofluidic channels, as well as open microfluidic systems with morethan one open interface (e.g. no channel “ceiling” nor “floor”).

The open microfluidic handling methods developed enable novel mechanismsto bring fluid into and out of the microfluidic network, and canincorporate methods including extracting fluid from a pool or droplet ona surface, such as human skin, from a reservoir, or from another openmicrofluidic channel. The design rules developed, made explicit by theSCF relation described in equation (1), allow the creation of opencapillary networks amenable to capturing blood pooling on the surface ofthe skin (as is the case for many diagnostic applications) andtransferring it into an open fluidic network. Additionally, it enablesthe design of open interconnection features allowing the transfer offluids from one open microfluidic network to another. The possibility ofextracting and exchanging fluids from one open microfluidic channel toanother enables the use of open microfluidic devices to create complexassays by assembling pre-fabricated standard building blocks or byleveraging 3D geometries simply by placing one open microfluidic networkon top of another, while allowing fluidic contacts from one network tothe other. Importantly, these methods can operate regardless of airbubble formation, as there is at least one open liquid-air interfacepresent in the channel, such as in a channel with a U-shapedcross-section containing no ceiling atop the microfluidic channel.Further, open microfluidic networks can leverage the open interface areato insert immiscible fluids or gases to sever the fluid present in thechannel in two sections. The ability of separating fluids in sectionsallows the creation of user actuated open microfluidic valves that arethe basis of advanced control over fluid flows in open microfluidicnetworks.

Shallow open microfluidic methods also enable the creation of fluidicnetworks that can be readily interfaces with traditional pipettingsystems in order to perform robotic interfacing with the microfluidicnetwork. The design guidelines developed also enable the creation ofmicrofluidic channels that have the ability to drive the flow of fluidusing only a subset of the walls of the channel and not the totality ofthe walls of the channel, such that the flow can be propelled aroundedges that would usually cause pinning. The flow pas pinning edges andlines further enables the creation of non-planar channels that flowaround concave and convex angles, or onto a new plane branching off ofthe main microfluidic channel. The design rules developed also allow thecapillary flow of a fluid over heterogeneous patches on the wall orfloor of the microfluidic channel. Such patches can include absorbentpads for capture of blood, reaction sites for detection of bloodanalytes, translucent materials for optical analysis of the blood, oropen apertures for physical access to the blood in the microfluidicchannel. Particularly, open apertures can be used to add or removesubstance from the channel, connected to a substance-specific removalarea (e.g. an organic solvent for chemical extraction, antibody-ladenhydrogel for detection, magnet for magnetic bead removal), or a large,set volume opening for contact with another open fluid or extractionmethod.

The other important aspects of the open microfluidic handling methodspertain to handling techniques of fluid within the microfluidic network.Because a specific set of design constraints can be used to create flowwithin a microfluidic network, they can also be leveraged to createunique functionality within the open microfluidic network that otherwisecould not be achieved with closed microfluidic systems or other openmicrofluidic systems.

A first general implementation enabled by open microfluidic systemspertain to the unique ability to pin a fluid in a channel devoid of aceiling. The design guideline provides precise geometrical rules fordescribing the conditions of flow in an open microfluidic channel, andby corollary the conditions for which flow cannot occur in an openmicrofluidic channel. Thus a channel can be designed such that at acertain location the conditions for flow are conditionally met based ona user-actuated system.

The second general set of implementations pertains to manipulating thechannel walls or creating unique flow environments within the openmicrofluidic network. These methods can include flowing the fluid overan aperture in the floor of the channel such that the fluid does not pinat this surface, placing a dried substance on the walls of the channelsuch that a fluid flows therein and incorporates the substance into thefluid, creating a mechanism for capillary pulling of fluid from one ofthe open channel to the other, directing fluid to multiple planes at anyangle, or a mechanism for allowing asynchronous fluids from variouschannels to incorporate into a larger channel or chamber without airbubble formation or dissipation. The latter method is enabled by theopen microfluidic environment as two fluids present in the channel atany location will not provoke the entrapment of an air bubble, as gaswill be able to escape through the open liquid-air section, thus the twofluids coming from either input channel in the branching area can mergewithout risking catastrophic failure of the microfluidic system.Additionally, the open microfluidic approach enables the connection ofmultiple networks together without risking the entrapment of air bubblesthat prevent further use of the microfluidic network.

All of these methods can be used to create complex fluidic networks thatcould be useful in a variety of applications, either in simplepoint-of-care devices (incorporating a dried or lyophilized sample intothe channel, combining multiple channels to a central location) or formore complex fluid networks, which can be interfaced with liquidhandling systems. Open networks are enabling for the reliability ofthese complex fluid networks, and further enhance the ability tofabricate channels in high throughput, as no bonding is necessary tocomplete device fabrication.

Referring generally to the figures, an “open microfluidic channel” isdefined as a channel with a cross-section containing one or moresections for which the fluid spans over an open air-liquid interface andone or more sections for which the fluid contacts a hydrophilicmaterial. The open microfluidic channel will also be referred to hereinas an open microfluidic channel, an open microfluidic network, an openmicrofluidic channel, a microfluidic channel, a microfluidic channel, ormore generally as a channel or a channel. It is understood that one ormore channels or channels can make up a network. At each point in themicrofluidic channel, the length of the section of the cross-sectioncontacting hydrophilic material is called the wetted perimeter, and thelength of the remaining section is called the free perimeter. Further,the SCF relation, determining whether spontaneous capillary flow occursin the open microfluidic channel, states that the ratio of the freeperimeter and the wetted perimeter of the microfluidic channel must beless than the cosine of the contact angle of the fluid on thehydrophilic material constituting the walls of the microfluidic channel.A microfluidic channel designed for performing a specific function orassembled with other microfluidic components is called an openmicrofluidic network.

By utilizing the open aspect of the microfluidic channel or channel aswell as surface tension phenomena, a variety of fluidic components canbe developed allowing the control of the flow through the microfluidicchannel and the creation of larger open microfluidic networks. Thedesign rule stating that the ratio of the free perimeter and the wettedperimeter of the microfluidic channel is less than the cosine of thecontact angle of the fluid, allows the design of microfluidic channelscontaining several open liquid-air interfaces, or channels that do notrequire the totality of the wetted perimeter to operate (and thus canstill flow if partly blocked by an air bubble or a ridge in thefabrication). Open microfluidic channel or microfluidic channels can bedesigned as a channel with a U-shaped cross-section devoid of a ceiling,or a channel with a rectangular cross-section devoid of a ceiling andfloor for example. Another example is a channel with a rectangularcross-section devoid of a ceiling and containing circular apertures inits floor. Certain other embodiments include channels with a V-shapedcross-section, trapezoidal cross-sections, rounded or multi-indentedcross-sections. These channel embodiments enable the design of channelsthat allow straightforward access for inserting or removing substancesfrom the microfluidic network.

Typical microfluidic approaches contain several inherent challenges thatlimit their reliability and ease-of-use for diagnostic, handheld, andanalysis applications. One of these challenges is the difficulty offabricating fully enclosed microfluidic channels, often requiring abonding step. Open microfluidic channels resolve this issue, as theyallow the creation of microfluidic networks that can be fabricated inone simple embossing step. A second challenge of typical microfluidicnetworks is the formation and entrapment of air bubbles, oftensynonymous of a critical failure of the whole microfluidic system. Acommon workaround involves the placement of air escapes to allow trappedair bubbles to escape, thus maintaining the fluidic connection withinthe microfluidic channel. Open microfluidic networks solve these priorart limitations by allowing at all locations air bubbles to escape.

A third challenge in prior art microfluidic systems is theinterconnection between the microscale channel and the macroscale realworld. In most traditional microfluidic systems, the fabrication of ausable device relies on establishing a water- or air-tight connectionbetween a tube leading into the microfluidic device and the deviceitself. Open microfluidic channels allow the input and output of fluidinto and from a channel by simply putting a drop of fluid in contactwith the channel or inserting a second open microfluidic network in afirst one. Further, open microfluidic channels enable the removal ofparticles from the fluid contained in the open microfluidic channel byleveraging the open interfaces for extraction by means of magnetic,diffusion, physical, or other interaction forces.

Referring now to the figures, the devices, systems and methodspertaining to the use of an open microfluidic network will be describedin detail. FIG. 1A- FIG. 1D are perspective views of various exemplaryembodiments of open microfluidic channels 11. These open microfluidicchannels 11 typically involve at least one free surface 12 and at leastone wetted surface 13 defining boundaries of a cross section 15 known asthe “free perimeter” (at 12) and “wetted perimeter,” (at 13)respectively. In certain exemplary embodiments, the cross-section 15 ofthe microfluidic channel 11 verifies the SCF relation stating that theratio of the length of the cross-section spanning over the at-least onefree surface 12 to the length of the cross-section spanning over theat-least one wetted surface 13 is less than the cosine of the contactangle 14A of the fluid 14 on the wetted surface 13, ensuring that fluid14 spontaneously flows by capillary force along channel 11.

The depicted embodiments are of a fluidic channel with one openinterface in a channel with a rectangular cross-section 15 (as shown inFIG. 1A), of a fluidic channel in a parallel rail embodiment 16 having afirst 12A and second 12B free surface, or interface (as shown in FIG.1B), of a fluidic channel with various free and wetted surfaces 17 (asshown in FIG. 1C), of a fluidic channel with a curved surface 18 and asecond contacting surface 19 (as shown in FIG. 1D), all of which allowfluid to freely flow within the channel 11. However, other embodimentsinvolving free surfaces 12 and wetted surfaces 13 can be enabled usingthis technique and can involve wedge channels, channels with apertures,channels with a V-shaped cross-section 20 (as shown in FIG. 1E),channels with a U-shaped cross-section 21 (as shown in FIG. 1F), andchannels with a rounded U-shaped cross section 21 a (as shown in FIG.1G), among others. Furthermore, the V-shaped cross-section depicted inFIG. 1E allows the creation of open microfluidic channels that allow thecapillary flow of fluids even with part of the wetted perimeter (shownat 13) impaired by factors such as an air bubble, a fabrication defect,or a local hydrophilic treatment defect.

In the exemplary embodiment depicted in FIG. 1H., the walls 23 a of anopen microfluidic channel 11 validate the design criteria alone suchthat they enable the flow over a ridge or fabrication defect 24 a, thatwould otherwise have caused the pinning of the fluid at that locationand thus the blockage of the channel. Other embodiments are possible.

FIGS. 2A-2D are perspective views of an open microfluidic channel 11that comes into contact with a pooling fluid 22 that exists on a surface23. The pooling fluid 22 can be blood, and the liquid can be pooling ona surface 23 such as the skin. By way of example, and as depicted inFIG. 2A, the open microfluidic channel 11 may contain a capture region24 and a channel region 25 that are connected and can allow the fluid 22to flow into the channel. The open microfluidic channel 11 is composedof free surfaces 12 and wetted surfaces 13 satisfying the SCF relation,stating that the ratio of the length of the cross-section of channel 11spanning over the at-least one free surface 12 to the length of thecross-section of channel 11 spanning over the at-least one wettedsurface 13 is less than the cosine of the contact angle of the fluid 14on the wetted surface 13.

The device embodiments described in FIGS. 2A-2C can be used, forexample, by placing the capture region 24 of the open microfluidicchannel 11 in contact with the pooling fluid 22 on a surface 23,allowing fluid to freely pull into the microfluidic channel 11. Uponcompletely removing the fluid, or when the user desires, the channel 11is disconnected from fluid 22 and the flow of fluid in the channelceases. In the embodiment described in FIG. 2D, an expanded open area 26is designed at the capture region 24 to facilitate the contact of theopen microfluidic network with the blood pooling on the surface.

In FIG. 2A, the capture region 24 and the channel region 25 arerepresented by an open channel devoid of a ceiling or top portion, theextremity of which can contact a fluid 22. The capture region 24 iswider than the channel region 25 in order to facilitate broad capture ofa pooling fluid. In alternative embodiments the walls of the captureregion 24 can be raised or extended to allow the creation of a widercaption region 24.

In the alternate embodiment described in FIG. 2B, the capture region 24is open near the surface 23 (or “bottom”) in order to facilitate thecapture of a pooling fluid 22. The channel region 25 is open away fromthe surface 23 (or “top”) in order to prevent the exposure of fluid tothe surface 23. The transition from the capture region 24 and thechannel region 25 may be comprised of a small section of channel openboth to the top and the bottom, by an immediate transition from open tothe top to open to the bottom, or by an overlapping region in which thechannel 11 is both closed on top and on bottom.

In the alternate embodiment described in FIG. 2C, the capture region 24is open to both the top and the bottom relative to the surface 23, thusallowing the capture of fluid 22, and connection to the channel region25 open only at the top, in order to prevent exposure of the fluid tothe surface 23. These embodiments may be developed with cross-sectionalgeometries of the channel 11, the channel region 25, or the captureregion 24, so as to provide a higher wetted surface 13. By way ofexample, such embodiments may include V-shaped, trapezoidal-shaped, orcrenated-shaped cross-sections.

FIG. 3A, FIG. 3B, FIG. 3C and FIG. 3D are various perspective views ofcertain embodiments of the open microfluidic channel 11 for use forremoving fluid or components of those substances from within an openmicrofluidic platform. FIG. 3A illustrates an open microfluidic channel11 with apertures 27 open to another environment, such as a solvent, anoil, a gas, a hydrogel, or another substance. The open microfluidicchannel 11 follows the SCF relation such that the ratio of the length ofthe cross-section of the channel 11-spanning over the at least one freesurface 12, including the opening of the aperture 27-to the length ofthe cross-section of channel 11-spanning over the at-least one wettedsurface 13-is less than the cosine of the contact angle of the fluid 14on the wetted surface 13. These embodiments allow any analytes presentin the fluid 14 flowing in the microfluidic channel to flow over theaperture 27, so that they may be extracted from, or viewed in the fluid14 through the apertures 27.

FIG. 3B is a perspective view of an embodiment of the open microfluidicchannel 11 further comprising a pad 28 in the center of the channel 11such that analyte fluid 22 or fluid 14 is extracted through the bottomof the channel as fluid 14 passes over the pad 28. It is understood thatcapillary flow occurs over the channel 11 (even in the absence of thepad 28), thereby ensuring a reliable connection between the fluid 14 inthe channel 11 and the pad 28.

FIG. 3C depicts a suspended channel 11 dipping into an open reservoir 29such that a fluid 14 is extracted from the reservoir 29 into the openmicrofluidic network (as designated by the channel 11).

FIG. 3D shows an alternate exemplary embodiment wherein a first openchannel 11 is placed within a second open channel 30, thus allowingfluid flowing down the first channel 11 to contact the second channel 30and flow along that second channel 30. Other embodiments facilitatingthe exchange of fluid between a first open microfluidic network and asecond microfluidic network can be devised. One concept is to have thewetted surfaces of the second microfluidic network extend over the freesurfaces of the first microfluidic network, such that the fluid can bedriven by spontaneous capillary flow in contact with the surfaces of thesecond network and subsequently the fluid can be flowed along the secondfluidic network. The latter embodiment can be achieved usinginterdigitated open microfluidic networks for instance.

FIG. 4A is a perspective view of an exemplary embodiment showing a fluid14 having a contact angle 14A entering the open microfluidic channel 11and flowing over a heterogeneous area 31 in the wetted surface 13 of themicrofluidic channel 11, which in various embodiments can be an openinterface, an absorbent pad, or an immiscible fluid. In theseembodiments, the open microfluidic channel 11 is designed to allow awetted surface 13 that can operate without a floor 32, thus allowingfluid 14 to flow over the heterogeneous patch 31. An analyte 33 can beextracted from the fluid 14 through contact with the heterogeneous patchby means of a capture mechanism which could be a hydrogel laden with acapture substance, a pad containing a capture substance, a magnet, oranother solid-phase capture system. The heterogeneous patch could alsobe a transparent material allowing optical access to the analyte 33dissolved in the fluid 14.

FIG. 4B is a perspective view of an embodiment of the heterogeneouspatch described in relation to FIG. 4A. In these exemplary embodiments,an aperture 34 connects the fluid 14 flowing in the channel 11 toanother fluidic or gaseous environment 35. This second fluidicenvironment 35 can be a specific liquid or gaseous phase to extract achemical component contained in the fluid 14 or a fraction of the fluid14, as desired.

FIG. 4C is a cross-sectional view of the embodiment in FIG. 4B.Illustrating the open microfluidic channel 11 with wetted surface 13 andtwo free surfaces 12, including the aperture 34. The fluid 14 is able toflow over the aperture 34 as the channel validated the SCF relationstating that the ratio of the length of the cross-section of channel 11spanning over the at-least one free surface 12, including the opening ofthe aperture 34, to the length of the cross-section of channel 11spanning over the at-least one wetted surface 13 is less than the cosineof the contact angle 14A of the fluid 14 on the wetted surface 13.

In the alternate embodiment depicted in FIG. 4D, magnetic beads 37 inthe fluid 14-used to bind an analyte of interest-are carried by thefluid 14 and extracted 38 into the environment outside of the channel bymeans of a magnetic force, as created by the magnetic beads 37 forinstance. Once extracted from the microfluidic channel, the beads out ofthe fluid 14 can be placed into a diagnostic device or equipment forchemical or molecular analysis. Other means of bead extraction arewell-known by those of skill in the art and can be incorporated into thedevice.

In the embodiment depicted in FIG. 4E, a fluid 14 flows over animmiscible fluid 39, at the location of the aperture 34. The contact ofthe two fluids allows the extraction of beads 38 through diffusion orother electrical forces, of an analyte 37 carried by the fluid 14. Oncein the immiscible phase, the analyte 33 can be removed from themicrofluidic network for subsequent analysis or flowed to an analysisregion or component.

FIG. 5A and FIG. 5B are perspective views of an exemplary embodimentcomprising an open microfluidic channel 11 controllably allowing fluidflow along its length depending on the position of a material closingpart of a free interface in the cross-section of channel 11. An openmicrofluidic channel, or network (shown at the channel 11), with aU-shape cross-section with hydrophilic walls (wetted surfaces 13) and anopen liquid-air interface (or free surface 12) on the ceiling validatesthe design criteria stating that the ratio of the length of thecross-section of channel 11 spanning over the at-least one free surface12, including the opening of the aperture 27, to the length of thecross-section of channel 11 spanning over the at-least one wettedsurface 13 is less than the cosine of the contact angle of the fluid 14on the wetted surface 13, allows a fluid to flow along its length. At acertain point in the length of the microfluidic channel thecross-section is changed such that it does not validate the SCF relationanymore. The change can be gradual or abrupt, such that the fluid stopsadvancing at a specific location along the channel 11. In the case of anabrupt change, a ridge 50 causes the pinning of the advancing fluid 14at a defined location. A displaceable material is allowed to move from aposition 51 non-contiguous to the open microfluidic channel, displayedin FIG. 5A, to a position 52 contiguous to the microfluidic channel,displayed in FIG. 5B. When the material is moved from the open position51 to the closed position 52, through the instruction of a user or anelectronic circuit, it is allowed to be in contact with the fluid 14flowing in the microfluidic channel, thus adding to the wetted perimeter(shown at 13) of the microfluidic channel and causing a variation of theratio of the free perimeter (shown at 12) to the wetted perimeter. Thesystem can be designed such that this ratio varies from a first valueless than the cosine of the contact angle of the fluid to a second valuehigher than the cosine of the contact angle of the fluid, thus enablingspontaneous capillary flow. Finally, the fluid 14, flowing in the openmicrofluidic channel, originally blocked in the channel when thematerial is positioned in the open position 51, can flow over thematerial when it is positioned in the closed position 52, and continuealong the open microfluidic channel 11. The material used to perform theswitching from a geometry not validating the SCF relation condition to ageometry validating the SCF relation and thus allowing spontaneouscapillary flow can be either a solid plastic, a hydrogel, or anothermiscible or immiscible fluid.

An alternative embodiment is shown in FIGS. 5C and 5D, in which thefluid 14 is stopped at a specific location (shown at 53A) in themicrofluidic channel wherein the geometry of the open microfluidicchannel does not validate the SCF relation, which states that the ratioof the length of the cross-section of the channel 11-spanning over theat-least one free surface 12, including the opening of the aperture27-to the length of the cross-section of the channel 11-spanning overthe at-least one wetted surface 13-is less than the cosine of thecontact angle of the fluid 14 on the wetted surface 13. When a useractuated force is imparted on the open microfluidic channel, displayedin FIG. 5C, causing the displacement of the walls 54 of the microfluidicchannel 11, displayed in FIG. 5D, the aforementioned ratio is decreasedto a value less than the cosine of the contact angle of the fluid in themicrofluidic channel, and the flow is allowed to continue along thelength of the channel 11 (as shown at 53B).

FIG. 6A is a perspective view of a fluid 14 flowing in an openmicrofluidic channel 11 starting at a first plane 60 and flowing aroundan angle or curved plane into a continuation of the microfluidic channelon a new plane 61 different from the first plane 60, according to oneimplementation. Importantly in embodiments such as the one shown in FIG.6A, the angle of the two planes is less than 180 degrees. In thisembodiment, the open microfluidic channel needs to satisfy the SCFrelation, which states that the ratio of the length of the cross-sectionof the channel 11 spanning over the at-least one free surface 12,including the opening of the aperture 27, to the length of thecross-section of the channel 11 spanning over the at-least one wettedsurface 13 is less than the cosine of the contact angle of the fluid 14on the wetted surface 13.

In implementations like that shown in FIG. 6B, the angle between thefirst plane 60 and the second plane 61 is more than 180 degrees.Specifically, this embodiment prevents the pinning of fluid at thecurvature line 62 by ensuring that the microfluidic channel 11 meets amore stringent SCF relation equivalent to that used for an openmicrofluidic channel devoid of both a ceiling and a wall or floor.Essentially, these embodiments allow the fluid 14 to flow past thecurvature line 62 by the capillary force provided by the walls of thechannel alone.

In implementations like that shown in FIG. 6C, a microfluidic channel 11open on top is defined on a planar surface 63, and is designed accordingto the aforementioned SCF relation, thus ensuring the flow of fluid inthe microfluidic channel. At a certain location in the first channel 11,a second microfluidic channel 64 build in a plane 65 intersects thechannel 11. The SCF relation allows the creation of a junction betweenthe first channel 11 and second channel 64 such that fluid can flow boththrough the first channel 11 and along the second channel 64. In orderto achieve this, the second channel 64 extends into the first channel 11using, at least in part, a channel that is devoid of both ceiling andfloor, such that the fluid can flow by capillary flow using the two sidewalls 66, 67. This system allows splitting the fluid flowing in themicrofluidic network between a microfluidic network with a certainfunction and a second microfluidic network stacked on top of the firstone and connected to it through a vertical open connector system.

FIG. 7A and FIG. 7B are perspective views of various exemplaryimplementations comprising an open microfluidic channel 11, which againvalidates the SCF relation-stating that the ratio of the free perimeterto the wetted perimeter is lower than the cosine of the contact angle,placed along a needle 70 that is designed to penetrate a membrane 71,such as the skin of a user or a membrane covering a reservoir of fluid.When the needle (originally non-contacting the membrane 71 as depictedin FIG. 7A), pierces the membrane 71 and accesses a fluid 14, such asblood or a reagent, the fluid 14 is able to flow into the microfluidicchannel 11 along the side of the needle 70, as depicted in FIG. 7B. Atthe base 72 of the needle 70, the needle contacts a surface 73containing an open microfluidic channel 74. These embodiments alsovalidate the SCF relation for the given fluid 14. The open microfluidicchannel 11 in the needle contact the open microfluidic channel 74 in thebase surface in the same plane or at an angled junction such that afluid 14 can flow along from the microfluidic channel 11 into themicrofluidic channel 74. The microfluidic network thus allows drawingfluid from a source protected by a membrane, through a tailored needle,and into an open microfluidic network containing other analysis,chemistry, or diagnostic fluidic components. Furthermore, such a systemallows the constant drawing of a fluid 14 into a microfluidic networkthat may have active or passive analysis components.

FIG. 8A and FIG. 8B depict perspective views of an open microfluidicchannel 11, according to certain implementations. In the implementationsof FIG. 8A and FIG. 8B, an open microfluidic channel 11 has across-section of the wetted surface 13 that progressively narrows from awide configuration end 80 to a narrow configuration end 81, as shown inFIG. 8A. At all points, however, the free surface cross sectional area12 to the wetted surface cross sectional area 13 is less than the cosineof the contact angle between the fluid to be flowed in the channel andthe wetted surface 13. As shown in FIG. 8B, when a droplet of fluid 82is placed in the microfluidic channel 11, a first side of the droplet(or “leading edge”) 83, facing towards the narrow end 81 of themicrofluidic channel 11, experiences a ratio of the free cross-sectionto the wetted cross section less than the second side of the droplet (or“the trailing edge”) 84, facing the wider end 80 of the channel 11. Insuch a system, a droplet of fluid 82, containing at least one openliquid-air interface, will self-propel through the microfluidic channel11, from the wider end 80 to the narrower end 81. Furthermore, in theseembodiments, this can be achieved with one or more open interfaces, suchas channels devoid of a ceiling, a ceiling and a floor, or channelsdevoid of a ceiling and containing apertures in the floor, as would beapparent to one of skill in the art.

In the embodiment depicted in FIG. 8C and FIG. 8D, the change ofgeometry along the channel length is not gradual, rather it containsfinite geometrical steps 85. In these exemplary embodiments, a dropletof fluid 82 inserted in the channel will equally flow along the channel11, towards the narrower end 81, provided that the geometries of thechannel are designed in such a way so as to allow the volume of thefluid to span from a step in the channel to the next step in thechannel.

In FIG. 8E, FIG. 8F and FIG. 8G, another embodiment is depicted whichallows the creation of open volume controlled valves that only permitfluid flow along a channel provided a sufficient amount of volume isinserted. In FIG. 8E, a droplet of fluid 82 is inserted into themicrofluidic channel 11, and through the mechanism described previously,it is able to self-propel forward as long as the ratio of free perimeterto wetted perimeter at the leading edge 83 is smaller than the ratio offree perimeter to wetted perimeter at the trailing edge 84. When thetrailing edge 84 reaches an abrupt change in geometry 86, if the leadingedge does not validate the condition described, the droplet of fluid 82stops.

FIG. 8F depicts the addition of an additional fluid 87 consisting of anaqueous fluid of similar surface energy, an aqueous fluid of lowersurface energy, or an immiscible fluid may be inserted into the channeland will itself flow down the channel 11 in a similar way as the firstdroplet of fluid 82. The open aspect of the channel will prevent airbubble formation in the channel as air can escape between the two fluids82 and 87 in the area 88.

As shown in FIG. 8G, if the additional fluid 87 is miscible with thedroplet of fluid 82 and contacts the original droplet of fluid 82, thevolume of the additional fluid adds to that of droplet and the increaseddroplet 89 may contain the sufficient volume to contact a subsequentgeometrical change 90. If the additional fluid 87 is immiscible with thedroplet of fluid 82 and contacts the original droplet of fluid 82, thetwo droplets connect but do not mix, and the fluid 87 propels the fluid82 beyond the constriction. With this method of self-microfluidicpropulsion, a channel 11 can be devoid of specialized geometries; solong as the immiscible back fluid 87 surface energy is less than theoriginal fluid 82. Once the droplet 89 contacts the geometrical change90, the whole droplet is able to flow forward into the microfluidicnetwork.

FIG. 9A, FIG. 9B, FIG. 9C, FIG. 9D and FIG. 9E are perspective views ofvarious embodiments of a first open microfluidic channel 11 with across-sectional wetted surface 13 that expands abruptly to a secondchannel 91 having a wetted perimeter 92, creating a pinning plane 93.Importantly, the two wetted perimeters-the first wetted surface 13 andsecond channel 91 wetted surface (shown at the flow 97, in FIG. 9E)-mustbe of different width and height, and both the first channel 11 andsecond channel 91 geometries must validate the SCF relation that theratio of the free surface cross sectional area 12 to the wetted surfacecross sectional area 13 as less than the cosine of the contact anglebetween the fluid 14 and the wetted surface 13.

As shown in the implementation of FIG. 9A, when a fluid 14 enters thefirst channel 11, the change in geometry causes fluid pinning on theplane 93. A fluid 94 inserted in the second channel 91 flows indirection of the first channel 11, as the air can escape from the openinterfaces 95 of the microfluidic channel, as shown in FIGS. 9B-9C. Uponcontact of the fluids 14 and 94, the pinning on plane 93 is released andthe fluid can then flow according to the natural pressure gradientgenerated by capillary force or any other pressure source, as depictedin FIGS. 9D-9E. Reversibly, if the first fluid to enter the network isfluid 94 in the channel 91, no pinning will be observed as the geometryis narrowing instead of increasing.

In the embodiment of FIG. 9D and FIG. 9E, a controllable open capillaryvalve is described. Similarly, a fluid 14 flowing down an openmicrofluidic channel 11 reaches an abrupt expansion in geometry, causingpinning of the fluid 14 at device plane 93, as depicted in FIG. 9D. Anopen area 96 allowing the manual or electronically controlled depositionof fluid is placed immediately after the plane 93. When a fluid is addedin the area 96, it removes the pinning of fluid 14 on plane 93 andallows the flow 97 to pursue along the channel according to the naturalpressure gradient, as shown in FIG. 9E. Conversely, when fluid 14 isremoved from area 96, a fluid from the open microfluidic channel 11 canonce again pin at the plane 93.

FIG. 10A and FIG. 10B are perspective views of embodiments comprising anopen microfluidic network 98 further comprising first and second openmicrofluidic channels 99, 100 combining into a single combinatorialarea, in this case a third channel 101. Each of the first channel 99,second channel 100, and third channel 101 further validate the SCFrelation that the ratio of the free surface cross sectional area 12 tothe wetted surface cross sectional area 13 as less than the cosine ofthe contact angle between the fluid 14 and the wetted surface 13 suchthat spontaneous capillary flow can occur. In these exemplaryembodiments, a fluid 102 entering the first channel 99 can flow down thechannel, reaches the intersection point between the first channel 99,second channel 100, and third channel 101, and is able to flow down thethird channel 101. In certain embodiments, a capillary valve such as isdepicted in FIG. 9A can be added to prevent flow down the second channel100.

In exemplary embodiments, a second fluid 103 can be added to the secondchannel 100, flow down the channel, without risk of trapping an airbubble as gas can escape through the open interfaces, as depicted inFIG. 10B. Once connected to the fluid 102 in the first channel 99, thesecond fluid 103 can combine volume to the volume of fluid 102 flowinginto the third channel 101 and create a resulting flow 104 comprised ofboth fluids 102, 103. These embodiments enable the creation of a devicecombining the fluid from multiple sources that may not deliver fluidsynchronously, without the risk of creating air bubbles, so as tocombine the liquids delivered by both sources. These embodiments canhave applications in mixing fluids in microfluidic networks or for moreefficient human bodily fluid collection from multiple sources.

FIGS. 10C, 10D and 10E depict alternate embodiments in which theconnection geometry 105 between the first 99 and second channels 100 isrounded in order to increase the ability of the first fluid 102 to fillthe combinatorial area/third channel 101. Similarly FIG. 10E, FIG. 10Fand FIG. 10G depict embodiments using open microfluidic channels thathave different profiles, such as the X-shaped cross section of FIG. 10E.By way of example, and as depicted in FIG. 10F and FIG. 10G, a V-shapedcross-section 106 allows more reliable connection of the fluids flowingdown the first 99 and second channels 100 into the third channel 101.The bottom edge 107 of the V-shaped cross-section enhances the capillarypull along both the connection of the first channel 99 to the thirdchannel 101, and the connection of the second channel 100 to the thirdchannel 101, as the fluid can follow the same single line connecting allthese channels together. This method can allow fluid to flow into anythird channel area 101, including an open microchannel, a pad, areservoir, or any other general area for fluid to congregate.

FIG. 11A and FIG. 11B are perspective views of alternate embodimentsenabling the flow of fluids from one open microfluidic channel toanother and reversibly in an approach that allows the building of openmicrofluidic networks by assembling standardized open microfluidiccomponents. In this method, the open microfluidic channel 11 is ended atan extremity 108 which would stop the flow of fluid due to pinning. Inthese embodiments, a second open microfluidic channel 109 is placed inclose proximity to the first channel 11 and fluid transfer from onechannel to the other is enabled through the addition of a structure 110connected to the second channel 109 and overreaching into channel 11. Asfluid is flowing by capillary force along the first channel 11, it isbrought in contact with the structure 110, which allows the fluid tobridge over the gap 111 and contact the wetted surfaces of channel 109.Reversibly, the structure 110 will enhance the ability of fluid flowingalong channel 109 to contact the walls of the first channel 11.

FIG. 11B is a perspective view of yet another alternate embodiment openmicrofluidic network inside a larger open microfluidic network. Thefirst channel 11 validated the SCF relation such that fluid 14 is ableto flow along its length by capillary force. The first channel 11 isbuilt inside a surface of a second open microfluidic channel 112, whichalso validates the SCF relation, allowing fluid 113 to flow along thelength of channel 112. In these embodiments, a first fluid can be flowninto the microfluidic network and be reacted, incubated, or acted upon,and a second carrier fluid or dilution fluid can be flown subsequently.Application of these embodiments may include the dilution a fluid sampleof interest such as blood, the insertion of a chemical reagent to reactwith the fluid sample of interest, or the deposition on the surfaces ofa microchannel of a chemical treatment that will react with a fluidsample of interest inserted in the larger channel. In the latter examplechemical reagents, such as lysis buffers or anti-clot factors, orsensing / capture materials, such as functionalized hydrogels ormagnetic beads, can be deposited.

FIG. 11C and FIG. 11D are perspective views of channel 11 embodimentsthat enable the flow of fluids from one open microfluidic channel 11 toanother in an approach that allows the building of open microfluidicnetworks that can be easily assembled and separated by standard openmicrofluidic components. In these implementations, the open microfluidicchannel 11 is ended at an extremity 114 which would stop the flow offluid due to pinning. A second open microfluidic channel or part of achannel 115 is placed in close proximity to the channel 11 and fluidtransfer from one channel to the other is enabled through the contact ofthe part of a channel 115 interior to the extremity 114. As fluid isflowing by capillary force along channel 11, it is brought into contactwith the channel 115, which allows fluid 113 to flow from channel 11into channel 116, enhanced by the contacting surface area of the channelor parts of a channel 115.

FIG. 11E and FIG. 11F are perspective views of an alternate embodimentwhich enables the flow of fluid 113 from one open microfluidic channelto another in an approach that allows the building of open microfluidicnetworks that can be easily assembled and separated by standard openmicrofluidic components. In this method the open microfluidic channel 11terminates at an extremity 117 which would stop the flow of the fluid113 due to pinning. This extremity 117 would have two openingspositioned directly across from each other in the channel 11. Aninterior structure 118a second microfluidic channel is placed directlythrough these two openings within channel 11 and fluid transfer from onechannel to the other is enabled through the contact of the part of achannel, which is an interior structure 118 to the extremity 117. As thefluid 113 flows by capillary force along channel 11, it is brought intocontact with the interior structure 118, which allows fluid to flow fromchannel 11 into channel 119, enhanced by the depth of the interiorstructure 118 interior to the extremity 117.

FIG. 12A, FIG. 12B and FIG. 12C are perspective views of variousalternative embodiments facilitating the flow of fluids from one openmicrofluidic channel into a larger volume reservoir in an approach thatallows the filling of an open microfluidic reservoir of variable volumesthat is accessible from at least one opening. In these embodiments, theopen microfluidic channel 11 enters a reservoir 120 that contains fluidcontact ridges 121 that enhance the surface area of the reservoir 120.These fluid contact ridges 121 may be spaced such that the fluid contactridges 121 would allow the fluid 113 to transfer from the openmicrofluidic channel 11 into the reservoir 120 and capillary forceswould maintain the fluid in the reservoir 120 enhanced by fluid contactridge number and surface area (as designated by the fluid contact ridges121).

FIG. 13A and FIG. 13B are perspective views of certain implementationsenabling the capture of excess fluid 113 on a surface 122 through openmicrofluidic channels 123 to dry or remove liquids in a simple way froma surface 122. In this method the open microfluidic channels 123 comeinto close proximity with the surface 122 such that the fluid 113 on thesurface 122 will come into contact with the channels 123 and be pulledinto the channels 123 and away from the surface 122.

FIG. 14A and FIG. 14B are perspective views of various embodiments of amethod enabling the application of a substance 124 to an openmicrofluidic channel 11 or reservoir 120 as a simple method to applytreatments to a contained fluid. This substance 124 may be dried orotherwise immobilized to a surface 125 that would comprise paper,plastic, rubber, or another material and would be placed on the channel11 or reservoir 120 bottom. In this method the substance 124 would betransferred to the channel 11 or reservoir 120 when fluid enters thearea, allowing the substance to dissolve into the fluid. In anotherembodiment, FIG. 14C and FIG. 14D depict the embodiments in which thesubstance 124 is dried or otherwise immobilized to a surface 125 thatwould comprise paper, plastic, rubber, or another material and would beplaced on the top of the channel 11 or reservoir 120. In theseembodiments, the substance 124 would be transferred to the channel 11 orreservoir 120 when fluid is already contained in the area when thesurface 125 contacts the fluid within the channel 11 or reservoir 120.

FIG. 15 is a perspective view of an exemplary embodiment of a handhelddevice 130. It is understood that various device and system embodimentsdisclosed herein, including the handheld device 130 of FIG. 15 , can beused for a variety of medical procedures and tasks including, but notlimited to, bodily fluid collection and analysis. For example, as shownin FIG. 15 in accordance with one embodiment, the handheld device 130contains a body 132 with a proximal end 134 and distal end 136. Aplunger 138 rests between the proximal end 134 and the distal end 136.According to one implementation, the body 132 defines a lumen 142 (asbest shown in FIG. 16 ) disposed through the body 132, such that thebody 132 in certain embodiments is considered a “hollow body” 132). Thebody 132 may be cylindrical in shape as illustrated in FIG. 15 , howeverother shapes such as oval, square, triangular, and the like may bereadily used as well. Further, the lumen 142 can also be cylindrical,oval, square, triangular, or any other known shape for a lumen. Theplunger 138 is disposed in the lumen 142 between the proximal end 134and the distal end 136 of the body 132, such that its displacement maybe controlled by a user-imparted force. It is understood that the deviceembodiments disclosed herein can also be used with any other knownsystem.

FIG. 16 is an exploded perspective view of an exemplary embodiment ofthe handheld device 130 on its side, in accordance with oneimplementation. The handheld device 130 contains the body 132 with theproximal end 134 and the distal end 136. The plunger 138 fits into theproximal end 134 of body 132, and a base 140 attaches to the distal end136 of the body 132. The body 132 defines a lumen 142 extendinglongitudinally, in some implementations, from the distal end 136 to theproximal end 134. According to one aspect, the lumen 142 can also beknown as a “vacuum creation space” 142. The body 132 also has a spring144 and a membrane tethering area 146. To use the handheld device 130, auser places the handheld device 130 on a subject’s skin, creating aseal. In an alternative embodiment, an adhesive is attached to thedistal end 136 of the handheld device 130 to adhere the handheld device130 to the subject’s skin and create a seal.

In these exemplary embodiments, when a user actuates the handheld device130 by imparting a force on the plunger 138, the plunger 138 isdisplaced towards the distal end 136 of the body 132 through the lumen142. Once the plunger 138 reaches its full displacement, a mechanism forretracting the plunger 138 is triggered. In the embodiment shown in FIG.16 , the mechanism for retracting the plunger 138 is the spring 144. Inan alternative embodiment, a membrane may be attached to the membranetethering area 146, and the membrane may be used to retract the plunger138. The mechanism for retracting the plunger 138 may be activated bythe user’s manual removal of the user-provided force on the plunger 138.In an alternative embodiment, when the user-imparted force pushes theplunger 138 past a trigger point, an internal mechanism in the handhelddevice 130 is triggered, activating the mechanism for retracting theplunger 138.

FIG. 17 is another exploded perspective view of an exemplary embodimentof the handheld device 130, in accordance with one implementation. Theplunger 138 is configured to be inserted into the lumen 142 at theproximal end 134 of the body 132 and contains a face 148 and a pluralityof needles 150. The plurality of needles 150 is fixed to the face 148.The base 140 attaches to the distal end 136 of the body 132 and containsa plurality of apertures 152 that are in fluid communication with thelumen 142 and match with the needles 150 on the plunger 138. Theplurality of needles 150 may include needles having a gauge from 140gauge to 40 gauge. In some embodiments, the needles are from 29 gauge to40 gauge. In an alternative embodiment, the plurality of needles 150 mayinclude a plurality of microneedles. In the embodiment shown in FIG. 17, the plurality of apertures 152 on the base 140 illustratively includesfour apertures. In alternative embodiments, the plurality of apertures152 may include from two to one hundred apertures. The plurality ofneedles 150 is aligned to be guided to pass through the plurality ofapertures 152 when a user actuates the handheld device 130.

FIG. 18 is an exploded front view of the handheld device 130, inaccordance with one implementation, and FIG. 19 is an exploded crosssectional front view of the handheld device 130, respectively, inaccordance with one implementation. In these and other exemplaryembodiments, each of the plurality of apertures 152 on the base 140defines a fluid extraction site. The plurality of needles 150 is fixedto the face 148 of the plunger 138 and configured such that when a useractuates the handheld device 130, the plunger 138 is urged distally andthe plurality of needles 150 is guided through the plurality ofapertures 152 on the base 140, and at least one of the plurality ofneedles 150 penetrates the subject’s skin to release bodily fluid. Atleast one of the plurality of needles 150 penetrate a subject’s skin ata low velocity and as a result, not all of the plurality of needles 150will necessarily penetrate the subject’s skin. All of the plurality ofneedles 150 may penetrate the skin. However, even when less than all ofthe plurality of needles 150 penetrate a subject’s skin, the handhelddevice 130 achieves high extraction reliability and is able toaccommodate not all of the plurality of needles 150 penetrating thesubject’s skin, as there are multiple fluid extraction sites, orapertures 152 from which the plurality of needles 150 can draw bodilyfluid.

By increasing the number of the plurality of needles 150, the handhelddevice 130 increases the probability of extracting a proper amount ofbodily fluid. The configuration of the plurality of needles 150 therebyensures bodily fluid extraction but without as much pain as is caused bya single, high velocity needle used in typical handheld fluid extractiondevices or array devices. This approach also lowers the variabilityinduced by the number of capillaries present at various locations on thesubject’s skin and differences or defects in the manufacturing of theplurality of needles 150. Additionally, the low velocity needlepenetration allows a simple design for the handheld device 130, as lowvelocity needle penetration requires fewer mechanical parts than atypical high velocity device.

In one embodiment, bodily fluid extracted by the plurality of needles150 may be blood. In another embodiment, bodily fluid extracted may beinterstitial fluid. Once bodily fluid is extracted from the subject andbegins to pool on the subject’s skin, the mechanism for retracting theplunger 138 is activated. The spring 144 retracts the plunger 138through the lumen 142 from the distal end 136 to the proximal end 134 ofthe body 132, removing the plurality of needles 150 from the subject’sskin and creating a vacuum in the vacuum creation space in the lumen142, which is the portion of the lumen 142 distal to the plunger 138. Inan alternative embodiment, a membrane (not shown) may be attached to themembrane tethering area 146, and the membrane retracts the plunger 138from the distal end 136 to the proximal end 134 of the body 132 throughthe lumen 142, removing the plurality of needles 150 from the subject’sskin and creating a vacuum in the lumen 142 distal to the plunger 138.The vacuum created in the lumen 142 creates a vacuum at each of thefluid extraction sites, or apertures 152, thereby enhancing the poolingof bodily fluid on the subject’s skin, optimizing fluid extraction fromeach puncture site where one of the plurality of needles 150 penetratesthe subject’s skin, and at the same time minimizing the size of eachpuncture site. The vacuum created may be from greater than 0 Pa to75,000 Pa.

FIG. 20 is an isometric view of the bottom of the base 140 of thehandheld device 130 according to an exemplary embodiment. FIG. 21 is aperspective view of the top of the base 140 of the handheld device 130according to an exemplary embodiment. In various embodiments, the base140 contains the plurality of apertures 152, at least one sensing area156, and a network of passages 154 in fluidic communication with theplurality of apertures 152 and the at least one sensing area 156, all ofwhich are in fluidic communication with the lumen 142. In variousembodiments, the needles (no shown) are able to slide through theapertures 152 so as to puncture the skin of the subject and cause bodilyfluid to pool on the subject’s skin. In the embodiments shown in FIG. 20and FIG. 21 , the network of passages 154 includes microfluidic channelsthat promote the pooled fluid to be directed toward the at least onesensing area 156 for collection and analysis. In exemplary embodiments,each of the plurality of apertures 152 is a part of such microfluidicchannels. In alternative embodiments, the network of passages 154 mayinclude tubes or paper channels.

When a user actuates the handheld device 130, resulting in bodily fluidpooling in at least one of the fluid extraction sites defined by theplurality of apertures 152 in the base 140, the network of passages 154collects the bodily fluid pooling on the surface of the subject’s skinfrom at least one of the fluid extraction sites. The network of passages154 collects bodily fluid from any fluid extraction site in which fluidextraction by the plurality of needles 150 was successful. In theembodiment shown in FIG. 20 and FIG. 21 , the network of passages 154directs collected bodily fluid by capillary action to the at least onesensing area 156 on the base 140 for analysis. The at least one sensingarea 156 collects the bodily fluid transported by the network ofpassages 154 and performs a sample preparation step. In one embodiment,the sample preparation step consists of filtration of erythrocytes ofother constituents of the blood. In alternative embodiments, the samplepreparation step may consist of bio-chemical labeling, cell-lysis, abio-chemical reaction, or separation of the bodily fluid into differentsub-components.

FIG. 22 is a perspective view of a portion of the top of the base 140 ofthe handheld device 130 according to various embodiments. This portionof the top of the base 140 contains part of the network of passages 154,part of one of the plurality of apertures 152, defining part of a fluidextraction site, or aperture 152, and at least one sensing area 156. Inthis embodiment, a passage 154 of the network of passages 154 includes aU-shaped channel within a hydrophilic material such that thechannel-fluid interface defining the wetted perimeter is larger than theliquid-air interface, defining the free perimeter. Bodily fluid is movedin a non-planar three-dimensional channel, allowing bodily fluidcollection and analysis in at least one sensing area 156 to occur ondifferent levels without increasing fabrication costs. Additionally,reliability is increased, as air bubbles do not cause fluid flowfailure. In alternative embodiments, the geometry of each of thepassages in the network of passages 154 may be varied to allow bodilyfluid handling using one-way valves, passive fluid pumps, specificvolume isolation for analysis, interfaces with a pad, and combinatorialflows.

While certain embodiments have been illustrated and described, it shouldbe understood that changes and modifications can be made therein inaccordance with ordinary skill in the art without departing from thetechnology in its broader aspects as defined in the following claims.

The embodiments, illustratively described herein may suitably bepracticed in the absence of any element or elements, limitation orlimitations, not specifically disclosed herein. Thus, for example, theterms ‘comprising,’ ‘including,’ ‘containing,’ etc. shall be readexpansively and without limitation. Additionally, the terms andexpressions employed herein have been used as terms of description andnot of limitation, and there is no intention in the use of such termsand expressions of excluding any equivalents of the features shown anddescribed or portions thereof, but it is recognized that variousmodifications are possible within the scope of the claimed technology.

Although the disclosure has been described with reference to preferredembodiments, persons skilled in the art will recognize that changes maybe made in form and detail without departing from the spirit and scopeof the disclosed apparatus, systems and methods.

The present disclosure is not to be limited in terms of the particularembodiments described in this application, which are intended asillustrations of various aspects. Many modifications and variations canbe made without departing from its spirit and scope, as will be apparentto those skilled in the art. Functionally equivalent compositions,apparatuses, and methods within the scope of the disclosure, in additionto those enumerated herein, will be apparent to those skilled in the artfrom the foregoing descriptions. Such modifications and variations areintended to fall within the scope of the appended claims. The presentdisclosure is to be limited only by the terms of the appended claims,along with the full scope of equivalents to which such claims areentitled. It is to be understood that this disclosure is not limited toparticular methods, reagents, compounds compositions or biologicalsystems, which can, of course, vary. It is also to be understood thatthe terminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting.

Other embodiments are set forth in the following claims.

1. (canceled)
 2. A method of collecting bodily fluid from a subject, themethod comprising: positioning a lower surface of a base of a bodilyfluid collection device against skin of the subject, wherein the basehas an aperture extending therethrough; actuating an actuation member ofthe bodily fluid collection device to move a skin-piercing feature ofthe bodily fluid collection device at least partially through a lumen ofthe bodily fluid collection device and at least partially through theaperture to puncture the skin of the subject; receiving the bodily fluidthrough the aperture; receiving the bodily fluid along a fluidic pathfluidly connected to the aperture such that the fluidic path directs thebodily fluid away from the aperture, wherein the fluidic path extends atleast partially in a direction parallel to the lower surface; andproviding vacuum pressure within the lumen such that the vacuum pressureis applied through the aperture.
 3. The method of claim 2 whereinproviding the vacuum pressure comprises activating a vacuum sourcepositioned at least partially within the lumen.
 4. The method of claim 2wherein the lumen has a circular cross-sectional shape.
 5. The method ofclaim 2 wherein positioning the lower surface of the base against theskin of the subject comprises positioning the bodily fluid collectiondevice with a hand of the subject.
 6. The method of claim 2, furthercomprising retracting the skin-piercing feature through the aperture andinto the lumen after puncturing the skin of the patient.
 7. The methodof claim 2 wherein providing the vacuum pressure within the lumencomprises actuating the actuation member to actuate a flexible membranepositioned within the lumen to generate the vacuum pressure.
 8. Themethod of claim 2 wherein the bodily fluid is blood.
 9. The method ofclaim 2 wherein the fluidic path at least partially comprises a fluidicchannel.
 10. The method of claim 9 wherein the fluidic channel is amicrofluidic channel.
 11. The method of claim 9 wherein the fluidicchannel is at least partially formed in the base within with the lumen.12. A method of collecting bodily fluid from a subject, the methodcomprising: positioning a lower surface of a base of a bodily fluidcollection device against skin of the subject, wherein the base has anaperture extending therethrough; and actuating an actuation member ofthe bodily fluid collection device to (a) provide vacuum pressure withina lumen of the bodily fluid collection device such that the vacuumpressure is applied through the aperture and (b) move a skin-piercingfeature of the bodily fluid collection device at least partially throughthe lumen and at least partially through the aperture to puncture theskin of the subject such that— the bodily fluid is received through theaperture and along a fluidic path fluidly connected to the aperture,wherein the fluidic path extends at least partially in a directionparallel to the lower surface; and the fluidic path directs the bodilyfluid away from the aperture.
 13. The method of claim 12 whereinproviding the vacuum pressure comprises activating a vacuum sourcepositioned at least partially within the lumen.
 14. The method of claim12, further comprising retracting the skin-piercing feature through theaperture and into the lumen after puncturing the skin of the patient.15. The method of claim 12 wherein providing the vacuum pressure withinthe lumen comprises actuating the actuating member to actuate a flexiblemembrane positioned within the lumen to generate the vacuum pressure.16. The method of claim 12 wherein the fluidic path at least partiallycomprises a fluidic channel that is at least partially formed in thebase within with the lumen.
 17. A method of collecting bodily fluid froma subject, the method comprising: positioning a base of a bodily fluidcollection device against skin of the subject, wherein the base has anaperture extending therethrough; actuating an actuation member of thebodily fluid collection to move a skin-piercing feature of the bodilyfluid collection device at least partially through a lumen of the bodilyfluid collection and at least partially through the aperture to puncturethe skin of the subject; and actuating a flexible membrane positionedwithin the lumen to generate vacuum pressure within the lumen such thatthe vacuum pressure is applied through the aperture.
 18. The method ofclaim 17 wherein flexible membrane is positioned over the aperture. 19.The method of claim 17 wherein actuating the flexible membrane comprisesactuating the actuation member.
 20. The method of claim 17, furthercomprising: receiving the bodily fluid through the aperture; andreceiving the bodily fluid along a fluidic path fluidly connected to theaperture such that the fluidic path directs the bodily fluid away fromthe aperture, wherein the fluidic path extends at least partially in adirection parallel to the lower surface.
 21. The method of claim 20wherein the fluidic path at least partially comprises a fluidic channelat least partially formed in the base within with the lumen.